Incorporation of second‐tier tests and secondary biomarkers to improve positive predictive value (PPV) rate in newborn metabolic screening program

BackgroundNowadays, neonatal screening has become an essential part of routine newborn care in the world. This is a non‐invasive evaluation that evaluated inborn errors of metabolisms (IEMs) using tandem mass spectrometry (LC‐MS/MS) for the evaluation of the baby''s risk of certain metabolic disorders.MethodsThis retrospective study was conducted on 39987 Iranian newborns who were referred to Nilou Medical Laboratory, Tehran, Iran, for newborn screening programs of IEMs. We incorporated second‐tier tests and secondary biomarkers to improve positive predictive value (PPV).ResultsStatistical data were recorded via call interviewing in 6–8 months after their screening tests. The overall prevalence of IEM was 1:975. The mean age of all participants was 3.9 ± 1.1 days; 5.1% of participants were over 13 days and 7.7% were preterm or underweight. A total of 11384 (29.4%) of the cases were born in a consanguineous family. The type of delivery was the cesarean section in 8332 (51.3%) valid cases. The neonatal screening results had an overall negative predictive value (NPV) of 100% and the overall PPV of 40.2%. The false‐positive rate was 0.15%.ConclusionThis study showed a high incidence of metabolic disease due to a high rate of consanguineous marriages in Iran and indicated that incorporation of second‐tier tests and secondary biomarkers improves PPV of neonatal screening programs.     

Dysgerminoma in a 15 years old phenotypically female Swyer syndrome with 46, XY pure gonadal dysgenesis: A case report

Swyer syndrome is a 46, XY karyotype, with pure gonadal dysgenesis and primary amenorrhea. These females have primordial Mullerian structures and seek medical attention as they experience primary amenorrhea. Here, we report a 15‐year‐old girl, diagnosed as Swyer syndrome associated with left ovarian dysgerminoma.     

Assessment of the response to chemotherapy in gestational trophoblastic neoplasia with vaginal metastases

Background and goals  This study is designed to survey gestational trophoblastic neoplasia with vaginal metastases (GTN + VM) manifestations, prognosis and chemotherapy response in order to consider appropriate chemotherapy regimen for these patients. There have been just a few studies about treatment of GTN + VM. Materials and methods  Patients with Stage III GTN with or without vaginal metastases who had referred to Vali-e-Asr Hospital during 1996–2006 have been selected to take part in this study and the size of metastases was measured. Then response and resistance to single and combination chemotherapy regimens have been compared in these two groups. The data were processed using SPSS system (release 10). Statistical analysis was done with X² to determine factors associated with complete clinical response. The level of significance was assigned at P < .05. Results  Forty-eight patients with stage III (with pulmonary metastases) GTN patients have been selected, 13 with vaginal metastases and 35 without vaginal metastases. Incidence of vaginal metastases in stage III was 26%. Metastases were mainly in distal part of vagina and suburethra. Chief complaint was severe hemorrhage in 25% of patients and was controlled by vaginal packing with just one exception. Group of vaginal metastases showed 66.6% resistance to first-line chemotherapy, compared to 28.6% in patients with no vaginal metastases (P-value = 0.010). Median of chemotherapy courses in low-risk vaginal metastatic patients was 5 (mean = 5.2), compared to three courses in the group without vaginal metastases. Resistance to single chemotherapy was significantly higher in GTN + VM versus GTN without VM patients and resistance was higher especially in patients with metastases with more than 3 cm (in diameter). Conclusions  Vaginal metastasis with more than 3 cm in diameter is an important prognostic factor in GTN patients. There have higher risks for severe hemorrhage and resistance to single agent chemotherapy, so in these patients combination chemotherapy, with no regard to staging and scoring, would be a better choice. An erratum to this article can be found at     

Molecular Detection and Identification of Zoonotic Microsporidia Spore in Fecal Samples of Some Animals with Close-Contact to Human

Background: Microsporidia species are obligatory intracellular agents that can infect all major animal groups including mammals, birds, fishes and insects. Whereas worldwide human infection reports are increasing, the cognition of sources of infection particularly zoonotic transmission could be helpful. We aimed to detect zoonotic microsporidia spore in fecal samples from some animals with close – contact to human. Methods: Overall, 142 fecal samples were collected from animals with closed-contact to human, during 2012-2013. Trichrome – blue staining were performed and DNA was then extracted from samples, identified positive, microscopically. Nested PCR was also carried out with primers targeting SSU rRNA gene and PCR products were sequenced. Results: From 142 stool samples, microsporidia spores have been observed microscopically in 15 (10.56%) samples. En. cuniculi was found in the faces of 3 (15%) small white mice and 1 (10%) laboratory rabbits(totally 2.81%). Moreover, E. bieneusi was detected in 3 (10%) samples of sheep, 2 (5.12%) cattle, 1 (10%) rabbit, 3 (11.53%) cats and 2 (11.76%) ownership dogs (totally 7.74%). Phylogenetic analysis showed interesting data. This is the first study in Iran, which identified E. bieneusi and En. Cuniculi in fecal samples of laboratory animals with close – contact to human as well as domesticated animal and analyzed them in phylogenetic tree. Conclusion: E. bieneusi is the most prevalent microsporidia species in animals. Our results can also alert us about potentially zoonotic transmission of microsporidiosis.Key Words: Laboratory animals, Enterocytozoon bieneusi, Encephalitozoon cuniculi, Zoonotic transmission     

Differentiation of Wharton's jelly mesenchymal stem cells into neurons in alginate scaffold

Alginate scaffold has been considered as an appropriate biomaterial for promoting the differentiation of embryonic stem cells toward neuronal cell lineage. We hypothesized that alginate scaffold is suitable for culturing Wharton's jelly mesenchymal stem cells(WJMSCs) and can promote the differentiation of WJMSCs into neuron-like cells. In this study, we cultured WJMSCs in a three-dimensional scaffold fabricated by 0.25% alginate and 50 m M Ca Cl2 in the presence of neurogenic medium containing 10 μM retinoic acid and 20 ng/m L basic fibroblast growth factor. These cells were also cultured in conventional two-dimensional culture condition in the presence of neurogenic medium as controls. After 10 days, immunofluorescence staining was performed for detecting β-tubulin(marker for WJMSCs-differentiated neuron) and CD271(motor neuron marker). β-Tubulin and CD271 expression levels were significantly greater in the WJMSCs cultured in the three-dimensional alginate scaffold than in the conventional two-dimensional culture condition. These findings suggest that three-dimensional alginate scaffold cell culture system can induce neuronal differentiation of WJMSCs effectively.     

Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design,methods and initial experience

The Isfahan Healthy Heart Programme (IHHP) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases (CVD) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population. IHHP started late in 1999 and will be finished in 2005-2006. A primary survey was done to collect baseline data from interventional (Isfahan and Najaf-Abad) and reference (Arak) communities. In a two-stage sampling method, we randomly selected 5 to 10 percent of households from randomly selected clusters. Then individuals aged > or = 19 years were selected for the survey. This way, data from 12,600 individuals (6300 in interventional counties and 6300 in the reference county) was collected and stratified according to living area (urban vs. rural) and different age and sex groups. The samples underwent a 30-minute interview to complete validated questionnaires containing questions on demography, socioeconomic status, smoking behaviour, physical activity, nutritional habits and other behaviour regarding CVD. Blood pressure and body mass index (BMI) measurements were done and fasting blood samples were taken for two hours post load plasma glucose (2 hpp), serum (total, HDL and LDL) cholesterol and triglyceride levels. A twelve-lead electrocardiogram was recorded in all persons above 35 years of age. Community-wide surveillance of deaths, hospital discharges, myocardial infarction and stroke registry was carried out in the intervention and control areas. Four to five years of interventions based on different categories such as mass media, community partnerships, health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention. Considering the results of the baseline surveys, (assessments needed, the objectives, existing resources and the possibility of national implementation) the interventions were planned. They were set based on specific target groups like school children, women, work-site, health personnel, high-risk persons, and community leaders were actively engaged as decision makers. A series of teams was arranged for planning and implementation of the intervention strategies. Monitoring will be done on small samples to assess the effect of different interventions in the intervention area. While four periodic surveys will be conducted on independent samples to assess health behaviours related to CVD risk factors in the intervention and reference areas, the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death, fatal and nonfatal MI and stroke. The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study.     

Serum measures of iron status and HFE gene mutations in patients with hepatitis B virus infection

Aim: We tested associations between HFE mutations and hepatitis B virus (HBV) infection. We also explored measures of total body iron status and their association with chronic HBV infection. Methods: Serum measures of iron status and HFE mutations (C282Y, H63D, and S65C) were assessed in 344 Iranian patients with chronic HBV infection (214 asymptomatic carriers, 130 patients with chronic progressive liver disease [CPLD]) and 302 controls. Results: Frequencies of HFE mutations did not differ between patients with chronic HBV infection and controls (C282Y: P=0.9, H63D: P= 0.8, S65C: P=0.9). By logistic regression, advanced hepatic fibrosis was associated with HFE H63D mutation (OR=13.1, P=0.006; 95% CI=2.0-84.1). Higher levels of serum ferritin and transferrin saturation were observed in patients with CPLD than in healthy controls (P=0.0001 and 0.01, respectively, adjusted for age and sex). None of the serum iron measures was related to liver fibrosis stage or necroinflammatory grade. Conclusion: Serum iron measures are associated with chronic progressive hepatitis B. Carriage of HFE mutations is not associated with the presence of chronic HBV infection or values of serum iron measures in this population, although HFE H63D is associated with more advanced hepatic fibrosis.     

Compliance and satisfaction with deferasirox (Exjade®) compared with deferoxamine in patients with transfusion-dependent beta-thalassemia

Objective

The current standard option for iron chelation therapy (ICT) in transfusion-dependent patients with beta-thalassemia is deferoxamine (DFO). We aimed to compare the compliance with DFO vs. deferasirox (Exjade^®), a novel oral iron chelator, in patients with transfusion-dependent beta-thalassemia.

Methods

In this cross-sectional study, 220 patients from Southern Iran who were receiving DFO or Exjade^® for the last 2 years were investigated in 2012. Satisfaction, compliance, convenience, and life disturbances of the patients with ICT were evaluated. Assessments were performed at four different occasions during 1 year.

Results

According to the results, 114 patients received treatment with DFO and 106 patients were treated with Exjade^®. In comparison with the patients who were treated with DFO, those receiving Exjade^® reported a significantly higher rate of compliance and convenience (P < 0.05). However, no significant difference was observed between the two groups regarding their satisfaction (P > 0.05). In the DFO group, 44.9% of the patients reported irritation and pain at the injection site.

Conclusions

Considering higher rate of compliance and convenience with Exjade^® and the comparable efficacy of these two modalities of ICT documented in previous studies, Exjade^® can be used as a preferable choice of ICT in iron-overload patients with beta-thalassemia.